Preparation of methylene bis-amides



2,713,594 PREPARATION OF METHYLENE BIS-AMIDES Charles W. Sauer, Cambridge, Mass., assignor to Arthur D. Little, Inc., Cambridge, Mass, a corporation of Massachusetts No Drawing. Application December 7, 1950, Serial No. 199,720

13 Claims. (Cl. 260558) This invention relates to the production of methylene bis-amides.

Prior to this invention relatively poor yields had been obtained in the preparation of methylene bis-amides, and methylene diformamide in particular. For instance, methylene diformamide is obtainable in about a 30% yield by reacting paraformaldehyde with formamide with the attendant production of water and loss of formaldehyde. Formaldehyde is given off during the reaction, and such evolution is disadvantageous.

It is an object of this invention to prepare methylene bis-amides without the incidental release of formaldehyde.

Another object is to prepare methylene bis-amides in good yields.

These, and other objects which will become apparent, may be accomplished by reacting hexamethylene tetramine with an amide. The methylene bis-amide crystals formed may be removed and more hexamethylene tetramine and amide added to the mother liquor for further reaction.

The process may then be made a continuous one or a batch process.

During the reaction ammonia is given off and should be removed as formed. No water is formed during the reaction, and since none is employed in the reaction, side reactions are maintained at a minimum, resulting in very good yields. It is essential, therefore, that hexamethylene tetramine be used as the source of formaldehyde. Formaldehyde or paraformaldehyde react with amides to yield water rather than ammonia in the course of the reaction.

For reasons that are not clear the excellent yields of this process are not apparent after the first reaction takes place, but only occur when a mother liquor is formed and new material is added to it.

Since it is easier to carry out the reaction when the reactants are in solution, a solvent may be added if the particular amide is not a solvent for the hexamethylene tetramine, and if the temperature is to be controlled by means other than refluxing the solvent. Typical solvents are dimethylformamide, quinoline and diethylcarbitol. Aqueous solutions are to be avoided as are any materials which will enter into the reaction to any appreciable extent. Once the mother liquor is formed no further solvent need be added as the reactants are soluble in the mother liquor.

Hexamethylene tetramine is reacted With'a compound having the formula NHzCOR where R is hydrogen, alkyl, cycloalkyl, substituted alkyl, heterocyclic, or aryl. As described in the examples below, it is evident that the R group does not enter into the reaction unless it contains a terminal group -NH2. Thus alkyl, aryl, cycloalkyl, and heterooyclic groups may be employed as the R group as desired. Substituted alkyl groups such as aralkyl may similarly be employed. Substituted alkyl groups such as malonamide O (NHzii-OHz-iiNHz) may also be used as shown in Example IV below, but such bifunctional materials should be used in one-half the molar quantities required of the monofunctional compounds.

tron with urea appears to be very complex and is not clearly understood. Urethanes, or esters of carbamic If one, or both, of the hydrogen atoms attached to the nitrogen atom in the above formulation are replaced as by an alkyl radical the reaction will not go. N-methyland may be employed to advantage.

The reaction of hexamethylene tetramine and the amide at least after the initial reaction is best carried out in the approximate molar ratios in which they react. I

give a theoretical yield of replacement of methylene bis-amide recovered by the first run. That is, if one secured.

Very high yields, through the replacement of methyltial yield, based on hexamethylene tetramine, is raised from about 30%, obtained by reacting equivalent quantities, to about 66%. Subsequent addition of equimolar quantities equivalent to the amount of methylene diformamide obtained increases the total yield in the order of about 540% above the initial yield. This method might be preferred in some instances.

The temperature, at which the process is carried out, is

to proceed. Dimethylformamide, having a boiling point of 153 C., diethylcarbitol 188 C., and quinoline 238 C., are all satisfactory, and indicate acceptable temperatures of operation.

The time necessary to complete the reaction will vary with varying conditions, but a good indication of completion is the absence of release of ammonia.

-More or less standard provisions for constant agitation of the mixture during reaction, removal of ammonia as formed, and refluxing of the solvent, are provided. Where a solvent having an extremely high boiling point is used, or where no solvent is employed, the temperature is regulated by conventional means.

4 and the white crystalline methylene-bis-malonamide melting at 234 C. recovered. The yield was 85.5% of theoretical.

As in the previous examples the mother liquor may advantageously be reused to maintain the high per cent To illustrate the unusually excellent yields obtainable yield values. by this process, the following example is given: Example V Example I Benzamide and hexamethylene tetramine were dissolved in quinoline in the ratio of twelve moles to one.

A mixture of 70 grams (0.5 mole) of hexamethylene The mixture was refluxed for 5 hours, and cooled to retetramine and 270 grams (6 moles) of freshly distilled cover white crystalline, methylene-bis-benzamide. The formamide were heated to 140 C. and maintained by melting point is 2l6220 C. The yield was 59% of regulation for four hours. On cooling, the crystals were theoretical in the first reaction. Repeated addition of separated, more benzamide and hexamethylene tetramine in the ratio The mother liquor was retained and to it was added of twelve moles to one to the mother liquor yields similar 23.5 grams (0.185 mole) of hexamethylene tetramine and results to those set forth in the prior examples.

90 grams (2 moles) of formamide. The mixture was The methylene derivatives described herein are useful maintained at 140 C. for five hours. The mixture Was intermediaries in the preparation of germicides. The cooled and the crystals separated. process is also adapted to the preparation of long chain The mother liquor was used in subsequent experiments polymers through the reaction with amides such as adipas above. The data on the yields is given below. amide.

Moles of Run Yield Total Yield Mother Hexa- Moles ff Run ii-$1 12 3 13 1: Form- Runs tetraamide Wt. Theo. Percent Wt. Theo. Percent Example 11 In general the ratio of one mole of hexamethylene 540 grams (12 m 0165) of formamide 140 grams (1 tetramine to twelve of a monofunctional and six of a bimole) of hexamethylene tetramine, and 500 cc. of diflmct10n?1.am1de 1S i l the lnltlal.reactlon methylformamide, were mixed and refluxed for 7 hours since this is the proportions 1n which the reaction takes The Solution was cooled and 180 grams (39.4%) of place. More or less of e1ther reactant may be employed methylene diformamide was recovered. but the.reactlng ratlos. are Prefe.rred' To the mother liquor was added 180 grams (4 moles) Havmg now descnbed P mventlon I 5 of formamide and 47 grams (.033 mole) of hexamethylprocess for prodqcnlg melhylene bls'amlde.s Whlch ene tetramine. The mixture was heated and refluxed for conslsts of the steps cllssolvmg both an amide and 6 hours, and cooled. 190 grams of methylene diformhefamethylene tetramme m nonfaqueous .solvent reamide was recovered (93% yield). actmg under anhydrous conditions 1n proportions so that Additions of similar amounts to the mother liquor were qllantlty. of Siamng .amlde Is least eqllal to the made, and Crystals of methylene diformamide recovered stoichlometrlc ratio requ1red to give two am1de groups many times. The yields resulting ran from 75% to 95% to i at a temperature above that.at of theoretical. wh1ch ammonla is given off and below that at which The purified product is a white crystalline material decpmposlilon of any of the reactants takes l Smd melting at l41l40 C. It is soluble in water to the extent am1de having the formlila.NHzcoR Wherem R 15 a of 100 grams in 109 cc. of water, and 6.6 grams in 100 cc. her i the group conslstmg of hyqrogen alkyl m ofisopmpanoL substituted alkyl, and aryl, removing the ammonla as Ex a mp1 6 1 formed, coollng the mixture and recovering crystalline methylene b1s-amide.

Hexamethylene tetramlne and acetamlde 1n the molar 2. The process according to claim 1 wherein the amide ratio of 1 to 12 were dissolved in quinoline and the mixi fo id refluxed for four From the 5011mm} 3 3. The process according to claim 11 wherein the amide y1eld of 32.4% of theoretical of methylene disacetamlde is acetamide. Was facovered' 4. The process according to claim 12 wherein the amide To the mother liquor was added an additional quantity is malonamide of hexarnethylene tetramme and acetamme 1n the same 5 h process according to claim 13 wherein the amide ratio as above; again the mixture was refluxed for four is benzamide 11011115 f q Yield of White crystalline methyl- 6. A process for producing methylene bis-amides which 6116 dlcetamlde meltlng at Was 90% of consists of the steps of dissolving both an amide and theorfitlfialhexamethylene tetramine in a non-aqueous solvent, reactreuse of the mother llqllof gave conslstenfly ing under anhydrous conditions in proportions so that hlgh y the quantity of starting amides is at least equal to the Example IV stoichiometric ratio required to give two amide groups Malonamide and hexamethylene tetramine in a ratio of to one g p at a temperature above that at 6 to 1 were mixed in dimethylformamide. The mixture Which ammonia is given Off and below that at Which was heated to dissolve the reactants in the solvent, and the decomposition of any of the reactants takes place, said solution refluxed for 6 hours. The solution was cooled amide having the formula NHzCOR wherein R is a memliquor as in the second methylene bis-amide formation, removing the crystals of methylene bis-amide when formed.

7. The process in accordance with claim 6 wherein the second and subsequent additions of hexamethylene tetramine and starting amide are equal to approximately the equivalent yield obtained in the first reaction.

8. The process in accordance with claim 6 wherein R is alkyl.

9. The process in accordance With claim 6 wherein R is aryl.

10. The process in accordance with claim 6 wherein R is amide-substituted alkyl.

11. A process for producing methylene bis-amides Which consists of the steps of dissolving an amide and hexamethylene tetramine in a non-aqueous solvent for both the amide and hexamethylene tetramine, reacting unto one CH2 grou at a temperature above that at which ammonia is given off and below that at which dethe ammonia as formed, cooling the mixture and recovering crystalline methylene bis-amide.

12. A process for producing methylene bis-amides which consists of the steps of dissolving an amide and hexamethylene tetramine in a non-aqueous solvent for both the amide and hexamethylene tetramine, reacting under anhydrous conditions in proportions so that the quantity of starting amide is substantially equal to the stoichiometric ratio required to give two amide groups to one CH2- group, at a temperature above that at c ratio required to give two amide groups to one CH2 group, at a temperature above that at which ammonia is given off and below that at which decomposition of any of the reactants takes place, said amide having ammonia as formed, cooling the mixture and recovering crystalline methylene bis-amide.

References Cited in the file of this patent UNITED STATES PATENTS Jahrstorfer et al. Oct. 19, 1937 DAlelio July 21, 1942 Graenacher Jan. 4, 1944 DAlelio June 20, 1944 Engelbrecht July 20, 1948 Lundberg July 12, 1949 FOREIGN PATENTS Great Britain May 25, 1939 France Nov. 12, 1938 OTHER REFERENCES Descude: Annales de Chimie, Series 7, vol. 29 (1903), p. 542.

Einhorn: Licbigs Annalen, vol. 361 (1908), pp. 150

and 151. 

1. A PROCESS FOR PRODUCING METHYLENE BIS-AMIDES WHICH CONSISTS OF THE STEPS OF DISSOLVING BOTH AN AMIDE AND HEXAMETHYLENE TETRAMINE IN A NON-AQUEOUS SOLVENT, REACTING UNDER ANHYDROUS CONDITIONS IN PROPORTIONS SO THAT THE QUANTITY OF STARTING AMIDE IS AT LEAST EQUAL TO THE STOICHIOMETRIC RATIO REQUIRED TO GIVE TWO AMIDE GROUPS TO ONE -CH2- GROUP, AT A TEMPERATURE ABOVE THAT AT WHICH AMMONIA IS GIVEN OFF AND BELOW THAT AT WHICH DECOMPOSITION OF ANY OF THE REACTANTS TAKES PLACE, SAID AMIDE HAVING THE FORMULA NH2COR WHEREIN R IS A MEMBER OF THE GROUP CONSISTING OF HYDROGEN, ALKYL, AMIDESUBSTITUTED ALKYL, AND ARYL, REMOVING THE AMMONIA AS FORMED, COOLING THE MIXTURE AND RECOVERING CRYSTALLINE METHYLENE BIS-AMIDE. 